**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** FOOD PRODUCTS RICH IN PROBIOTICS AND PLANT PHENOLICS HAVE SIGNIFICANT POTENTIAL TO IMPACT HUMAN GUT HEALTH. HOWEVER, LIMITED VIABILITY OF PROBIOTICS DURING DELIVERY TO THE GUT AND LACK OF PERSISTENCE OF THESE BACTERIA IN THE GUT SIGNIFICANTLY LIMITS THE IMPACT OF THESE PRODUCTS. SIMILARLY LACK OF PHYSICO-CHEMICAL STABILITY OF PLANT PHENOLICS DURING DELIVERY TO THE GUT AND LIMITED MICROBIAL METABOLISM OF PHENOLICS CAN SIGNIFICANTLY IMPACT THEIR BIOLOGICAL ACTIVITY. TO ADDRESS THESE CHALLENGES, OUR INTERDISCIPLINARY TEAM PROPOSES TO DEVELOP A SYNERGISTIC COMBINATION OF PROBIOTICS AND PLANT PHENOLICS BY INFUSING PHENOLIC COMPOUNDS INTO PROBIOTIC CELLS. THIS UNIQUE COMBINATION HAS A POTENTIAL TO ENABLE MULTIFOLD IMPROVEMENT IN THE DELIVERY OF PROBIOTICS TO THE GUT AND ENHANCED MUCO-ADHESION AS WELL AS ENHANCEMENT IN MICROBIAL METABOLISM OF PHENOLICS BASED ON OUR PRELIMINARY STUDIES. THE SPECIFIC OBJECTIVES ARE: (A) DISCOVER AND CHARACTERIZE THE ROLE OF PLANT PHENOLICS IN IMPROVING RESISTANCE OF DIVERSE PROBIOTIC BACTERIA TO GASTRO-INTESTINAL BARRIERS; (B) ROLE OF SYNERGISTIC COMBINATION IN ENHANCING MICROBIAL METABOLISM OF PHENOLICS AND MUCO-ADHESION OF PROBIOTICS; AND (C) IN-VIVO VALIDATION OF THE EFFICACY OF THE PROPOSED APPROACH IN ENHANCING PERSISTENCE OF PROBIOTICS AND REDUCING INFLAMMATION AND DYSBIOSIS. THE SUCCESS OF THIS PROJECT WILL SIGNIFICANTLY BENEFIT HUMAN HEALTH BY DEVELOPING A NOVEL FOOD-BASED APPROACHES TO DELIVER PROBIOTICS AND PHENOLIC BIOACTIVES THAT ENHANCES THE DELIVERY AND PERSISTENCE OF PROBIOTICS IN THE GUT AND PROMOTE GENERATION OF BIOACTIVE PHENOLIC METABOLITES AT A TARGET SITE (COLON) IN THE GUT. THE PROJECT ALSO ENABLES DEVELOPMENT OF VALUE-ADDED FOOD INGREDIENTS FROM SPENT FRACTIONS OF PLANT PRODUCTS.